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. 1994 Jun 21;91(13):5992–5996. doi: 10.1073/pnas.91.13.5992

Evolutionary selection against change in many Alu repeat sequences interspersed through primate genomes.

R J Britten 1
PMCID: PMC44123  PMID: 8016103

Abstract

Mutations have been examined in the 1500 interspersed Alu repeats of human DNA that have been sequenced and are nearly full length. There is a set of particular changes at certain positions that rarely occur (termed suppressed changes) compared to the average of identical changes of identical nucleotides in the rest of the sequence. The suppressed changes occur in positions that are clustered together in what appear to be sites for protein binding. There is a good correlation of the suppression in different positions, and therefore the joint probability of absence of mutation at many pairs of such positions is significantly higher than that expected at random. The suppression of mutation appears to result from selection that is not due to requirements for Alu sequence replication. The implication is that hundreds of thousands of Alu sequences have sequence-dependent functions in the genome that are selectively important for primates. In a few known cases Alu inserts have been adapted to function in the regulation of gene transcription.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailey W. J., Hayasaka K., Skinner C. G., Kehoe S., Sieu L. C., Slightom J. L., Goodman M. Reexamination of the African hominoid trichotomy with additional sequences from the primate beta-globin gene cluster. Mol Phylogenet Evol. 1992 Jun;1(2):97–135. doi: 10.1016/1055-7903(92)90024-b. [DOI] [PubMed] [Google Scholar]
  2. Blake R. D., Hess S. T., Nicholson-Tuell J. The influence of nearest neighbors on the rate and pattern of spontaneous point mutations. J Mol Evol. 1992 Mar;34(3):189–200. doi: 10.1007/BF00162968. [DOI] [PubMed] [Google Scholar]
  3. Brini A. T., Lee G. M., Kinet J. P. Involvement of Alu sequences in the cell-specific regulation of transcription of the gamma chain of Fc and T cell receptors. J Biol Chem. 1993 Jan 15;268(2):1355–1361. [PubMed] [Google Scholar]
  4. Britten R. J., Baron W. F., Stout D. B., Davidson E. H. Sources and evolution of human Alu repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4770–4774. doi: 10.1073/pnas.85.13.4770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Britten R. J., Davidson E. H. Gene regulation for higher cells: a theory. Science. 1969 Jul 25;165(3891):349–357. doi: 10.1126/science.165.3891.349. [DOI] [PubMed] [Google Scholar]
  6. Britten R. J., Davidson E. H. Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q Rev Biol. 1971 Jun;46(2):111–138. doi: 10.1086/406830. [DOI] [PubMed] [Google Scholar]
  7. Brosius J. Retroposons--seeds of evolution. Science. 1991 Feb 15;251(4995):753–753. doi: 10.1126/science.1990437. [DOI] [PubMed] [Google Scholar]
  8. Carlson D. P., Ross J. Human beta-globin promoter and coding sequences transcribed by RNA polymerase III. Cell. 1983 Oct;34(3):857–864. doi: 10.1016/0092-8674(83)90543-3. [DOI] [PubMed] [Google Scholar]
  9. Carlson D. P., Ross J. Point mutation associated with hereditary persistence of fetal hemoglobin decreases RNA polymerase III transcription upstream of the affected gamma-globin gene. Mol Cell Biol. 1986 Sep;6(9):3278–3282. doi: 10.1128/mcb.6.9.3278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chang D. Y., Maraia R. J. A cellular protein binds B1 and Alu small cytoplasmic RNAs in vitro. J Biol Chem. 1993 Mar 25;268(9):6423–6428. [PubMed] [Google Scholar]
  11. Chung J., Sussman D. J., Zeller R., Leder P. The c-myc gene encodes superimposed RNA polymerase II and III promoters. Cell. 1987 Dec 24;51(6):1001–1008. doi: 10.1016/0092-8674(87)90586-1. [DOI] [PubMed] [Google Scholar]
  12. Coulondre C., Miller J. H., Farabaugh P. J., Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. doi: 10.1038/274775a0. [DOI] [PubMed] [Google Scholar]
  13. Davidson E. H., Britten R. J. Organization, transcription, and regulation in the animal genome. Q Rev Biol. 1973 Dec;48(4):565–613. doi: 10.1086/407817. [DOI] [PubMed] [Google Scholar]
  14. Davidson E. H., Britten R. J. Regulation of gene expression: possible role of repetitive sequences. Science. 1979 Jun 8;204(4397):1052–1059. doi: 10.1126/science.451548. [DOI] [PubMed] [Google Scholar]
  15. Davidson E. H. Note on the control of gene expression during development. J Theor Biol. 1971 Jul;32(1):123–130. doi: 10.1016/0022-5193(71)90140-8. [DOI] [PubMed] [Google Scholar]
  16. Deininger P. L., Batzer M. A., Hutchison C. A., 3rd, Edgell M. H. Master genes in mammalian repetitive DNA amplification. Trends Genet. 1992 Sep;8(9):307–311. doi: 10.1016/0168-9525(92)90262-3. [DOI] [PubMed] [Google Scholar]
  17. Hambor J. E., Mennone J., Coon M. E., Hanke J. H., Kavathas P. Identification and characterization of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene. Mol Cell Biol. 1993 Nov;13(11):7056–7070. doi: 10.1128/mcb.13.11.7056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Howard B. H., Sakamoto K. Alu interspersed repeats: selfish DNA or a functional gene family? New Biol. 1990 Sep;2(9):759–770. [PubMed] [Google Scholar]
  19. Hull M. W., Erickson J., Johnston M., Engelke D. R. tRNA genes as transcriptional repressor elements. Mol Cell Biol. 1994 Feb;14(2):1266–1277. doi: 10.1128/mcb.14.2.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hutchinson G. B., Andrew S. E., McDonald H., Goldberg Y. P., Graham R., Rommens J. M., Hayden M. R. An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily. Nucleic Acids Res. 1993 Jul 25;21(15):3379–3383. doi: 10.1093/nar/21.15.3379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jurka J. A new subfamily of recently retroposed human Alu repeats. Nucleic Acids Res. 1993 May 11;21(9):2252–2252. doi: 10.1093/nar/21.9.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jurka J., Milosavljevic A. Reconstruction and analysis of human Alu genes. J Mol Evol. 1991 Feb;32(2):105–121. doi: 10.1007/BF02515383. [DOI] [PubMed] [Google Scholar]
  23. Jurka J., Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4775–4778. doi: 10.1073/pnas.85.13.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kato N., Shimotohno K., VanLeeuwen D., Cohen M. Human proviral mRNAs down regulated in choriocarcinoma encode a zinc finger protein related to Krüppel. Mol Cell Biol. 1990 Aug;10(8):4401–4405. doi: 10.1128/mcb.10.8.4401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kim J. H., Yu C. Y., Bailey A., Hardison R., Shen C. K. Unique sequence organization and erythroid cell-specific nuclear factor-binding of mammalian theta 1 globin promoters. Nucleic Acids Res. 1989 Jul 25;17(14):5687–5700. doi: 10.1093/nar/17.14.5687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. King C. C. Modular transposition and the dynamical structure of eukaryote regulatory evolution. Genetica. 1992;86(1-3):127–142. doi: 10.1007/BF00133716. [DOI] [PubMed] [Google Scholar]
  27. Leeflang E. P., Liu W. M., Hashimoto C., Choudary P. V., Schmid C. W. Phylogenetic evidence for multiple Alu source genes. J Mol Evol. 1992 Jul;35(1):7–16. doi: 10.1007/BF00160256. [DOI] [PubMed] [Google Scholar]
  28. Lo K., Landau N. R., Smale S. T. LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes. Mol Cell Biol. 1991 Oct;11(10):5229–5243. doi: 10.1128/mcb.11.10.5229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Matera A. G., Hellmann U., Hintz M. F., Schmid C. W. Recently transposed Alu repeats result from multiple source genes. Nucleic Acids Res. 1990 Oct 25;18(20):6019–6023. doi: 10.1093/nar/18.20.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matera A. G., Hellmann U., Schmid C. W. A transpositionally and transcriptionally competent Alu subfamily. Mol Cell Biol. 1990 Oct;10(10):5424–5432. doi: 10.1128/mcb.10.10.5424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McDonald J. F. Evolution and consequences of transposable elements. Curr Opin Genet Dev. 1993 Dec;3(6):855–864. doi: 10.1016/0959-437x(93)90005-a. [DOI] [PubMed] [Google Scholar]
  32. Morzycka-Wroblewska E., Harwood J. I., Smith J. R., Kagnoff M. F. Structure and evolution of the promoter regions of the DQA genes. Immunogenetics. 1993;37(5):364–372. doi: 10.1007/BF00216801. [DOI] [PubMed] [Google Scholar]
  33. Murphy M. H., Baralle F. E. Directed semisynthetic point mutational analysis of an RNA polymerase III promoter. Nucleic Acids Res. 1983 Nov 25;11(22):7695–7700. doi: 10.1093/nar/11.22.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Neznanov N. S., Oshima R. G. cis regulation of the keratin 18 gene in transgenic mice. Mol Cell Biol. 1993 Mar;13(3):1815–1823. doi: 10.1128/mcb.13.3.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Perez-Stable C., Ayres T. M., Shen C. K. Distinctive sequence organization and functional programming of an Alu repeat promoter. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5291–5295. doi: 10.1073/pnas.81.17.5291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Saffer J. D., Thurston S. J. A negative regulatory element with properties similar to those of enhancers is contained within an Alu sequence. Mol Cell Biol. 1989 Feb;9(2):355–364. doi: 10.1128/mcb.9.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sakamoto K., Fordis C. M., Corsico C. D., Howard T. H., Howard B. H. Modulation of HeLa cell growth by transfected 7SL RNA and Alu gene sequences. J Biol Chem. 1991 Feb 15;266(5):3031–3038. [PubMed] [Google Scholar]
  38. Saëgusa Y., Sato M., Galli I., Nakagawa T., Ono N., Iguchi-Ariga S. M., Ariga H. Stimulation of SV40 DNA replication and transcription by Alu family sequence. Biochim Biophys Acta. 1993 Mar 20;1172(3):274–282. doi: 10.1016/0167-4781(93)90214-x. [DOI] [PubMed] [Google Scholar]
  39. Schmid C., Maraia R. Transcriptional regulation and transpositional selection of active SINE sequences. Curr Opin Genet Dev. 1992 Dec;2(6):874–882. doi: 10.1016/s0959-437x(05)80110-8. [DOI] [PubMed] [Google Scholar]
  40. Shapiro J. A. Natural genetic engineering in evolution. Genetica. 1992;86(1-3):99–111. doi: 10.1007/BF00133714. [DOI] [PubMed] [Google Scholar]
  41. Sussman D. J., Chung J., Leder P. In vitro and in vivo analysis of the c-myc RNA polymerase III promoter. Nucleic Acids Res. 1991 Sep 25;19(18):5045–5052. doi: 10.1093/nar/19.18.5045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tomilin N. V., Bozhkov V. M., Bradbury E. M., Schmid C. W. Differential binding of human nuclear proteins to Alu subfamilies. Nucleic Acids Res. 1992 Jun 25;20(12):2941–2945. doi: 10.1093/nar/20.12.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Vidal F., Mougneau E., Glaichenhaus N., Vaigot P., Darmon M., Cuzin F. Coordinated posttranscriptional control of gene expression by modular elements including Alu-like repetitive sequences. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):208–212. doi: 10.1073/pnas.90.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wallace M. R., Andersen L. B., Saulino A. M., Gregory P. E., Glover T. W., Collins F. S. A de novo Alu insertion results in neurofibromatosis type 1. Nature. 1991 Oct 31;353(6347):864–866. doi: 10.1038/353864a0. [DOI] [PubMed] [Google Scholar]
  45. Weiner A. M., Deininger P. L., Efstratiadis A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem. 1986;55:631–661. doi: 10.1146/annurev.bi.55.070186.003215. [DOI] [PubMed] [Google Scholar]
  46. Wu J., Grindlay G. J., Bushel P., Mendelsohn L., Allan M. Negative regulation of the human epsilon-globin gene by transcriptional interference: role of an Alu repetitive element. Mol Cell Biol. 1990 Mar;10(3):1209–1216. doi: 10.1128/mcb.10.3.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. von Sternberg R. M., Novick G. E., Gao G. P., Herrera R. J. Genome canalization: the coevolution of transposable and interspersed repetitive elements with single copy DNA. Genetica. 1992;86(1-3):215–246. doi: 10.1007/BF00133722. [DOI] [PubMed] [Google Scholar]

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